1. Academic Validation
  2. A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation

A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation

  • iScience. 2021 Oct 16;24(11):103296. doi: 10.1016/j.isci.2021.103296.
Sheng Li 1 Leilei Zhang 1 Guoan Zhang 1 Guoqiang Shangguan 1 Xitan Hou 1 Wanglin Duan 2 Yan Xi 3 Nan Xu 3 Bowen Zhang 3 Junli Dong 3 Yequan Wang 1 Wen Cui 1 Su Chen 1 3 4
Affiliations

Affiliations

  • 1 School of Forensic Sciences and Laboratory Medicine, Jining Medical University, Jining, Shandong Province 272067, PR China.
  • 2 School of Forensic Sciences, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi Province 710061, PR China.
  • 3 Laboratory of Molecular and Cellular Biology, School of Basic Medical Sciences, Henan University School of Medicine, Kaifeng, Henan Province 475004, PR China.
  • 4 Department of Science and Education, People's Hospital of Zunhua, Tangshan, Hebei Province 064200, PR China.
Abstract

Autophagy is a conserved biological process that maintains cell homeostasis by targeting macromolecules for lysosome-mediated degradation. The levels of Autophagy are relatively lower under normal conditions than under stress conditions (e.g., starvation), as Autophagy is usually stimulated after multiple stresses. However, many autophagy-related regulators are still expressed under normal conditions. Although these regulators have been studied deeply in Autophagy regulation, the nonautophagic roles of these regulators under normal conditions remain incompletely understood. Here, we found that autophagy-related 5 (ATG5), which is a key regulator of Autophagy, regulates c-Myc protein degradation under normal conditions through the ubiquitin-proteasome pathway. We also found that ATG5 binds c-Myc and recruits the E3 ubiquitin-protein Ligase FBW7 to promote c-Myc degradation. Moreover, ATG5-mediated degradation of c-Myc limits cell growth under normal conditions and is essential for embryonic stem cell differentiation. Therefore, this study reveals a nonautophagic role of ATG5 in regulating of c-Myc protein degradation.

Keywords

Cell biology; Functional aspects of cell biology.

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